Structure of 3819-88-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 3819-88-3 |
Formula : | C6H3FINO2 |
M.W : | 267.00 |
SMILES Code : | O=[N+](C1=CC(I)=CC(F)=C1)[O-] |
MDL No. : | MFCD00007219 |
InChI Key : | MXPYCSFCKXSPAB-UHFFFAOYSA-N |
Pubchem ID : | 259086 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.94 |
TPSA ? Topological Polar Surface Area: Calculated from |
45.82 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.68 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.76 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.04 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.21 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.41 |
Solubility | 0.104 mg/ml ; 0.000391 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.11 |
Solubility | 0.208 mg/ml ; 0.00078 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.01 |
Solubility | 0.262 mg/ml ; 0.000982 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.15 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
3.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.45 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With tin(II) chloride dihdyrate; In ethanol; for 1.5h;Reflux; | Example 2Synthesis of 3-fluoro-5-iodo-N,N-dimethylaniline (VMY-2-119): The suspension of l-fluoro-3-iodo-5 -nitrobenzene (0.5 g, 1.87 mmol) and SnCl2'2H20 (1.5 g, 6.64 mmol) in EtOH (10 mL) was heated to reflux for 1.5 h. The solvent was removed and the crude mixture was diluted with ether, washed with 4 N NaOH and brine. The ether layer was- 42 -B4067289v2 separated and dried over Na2S04, filtered, concentrated to yield amine compound as a solid (0.4 g, 91%). The crude product was used without purification.A solution of above amine (0.4 g, 1.69 mmol) and iodomethane (0.719 g, 5 mmol) in dimethylformamide (DMF; 10 mL) containing potassium carbonate (0.46 g, 3.38 mmol) was stirred for 48 h at room temperature. Water (lOmL) was then added and the solution was extracted with ether three times. The organic extracts washed with water, brine, dried over Na2S04, filtered and concentrated. The crude product was purified by column chromatography to yield VMY-2-119 as a liquid (0.23 g, 52%). 1H NMR (399 MHz) ? 6.69 - 6.63 (m, 2H), 6.22 (dt, J = 12.5, 2.3, 1H), 2.83 (s, 6H). 13C NMR (100 MHz) ? 163.33(d, JF-C=245 Hz), 152.49(d, J=l lHz) 116.91 (d, J = 2.4), 112.12(d, J=24 Hz), 98.73(d, J=26Hz), 94.24(d, J=l l Hz), 40.21 (s, 3H). |
Production Example 341 3-Fluoro-5-iodophenylamine 3.2 g crude title compound (yellow oil) was obtained from 3.0 g of 3-fluoro-5-iodonitrobenzene by the same reaction as in Production Example 335.1H-NMR (CDCl3) delta: 3.78(brs, 2H), 6.28-6.35(m, 1H), 6.75-6.84(m, 2H) | ||
With iron; acetic acid; In tetrahydrofuran; water; at 40℃; | 3-Iodo-5-fluoro-1-nitrobenzene (5.2 g; 19.48 mmol) is dissolved in a 4/3 water/tetrahydrofuran mixture. Powdered iron (8.7 g; 156 mmol), followed by acetic acid (4.5 ml) are added at room temperature and the suspension formed is stirred overnight at 40 C. The reaction mixture is filtered over diatomaceous earth and poured on to water. The mixture is extracted with ethyl acetate and the combined organic phases are dried over sodium sulphate, filtered and concentrated. The residue is chromatographed over silica gel with n-hexane/ethyl acetate (3/1). The pure fractions are combined and the solvent is evaporated off. The residue is diluted with methylene chloride (30 ml), and pyridine (4,0 ml; 49.5 mmol) and trifluoroacetic anhydride (3.44 ml; 24.7 mmol) are added and the mixture is stirred for one hour at room temperature. The reaction solution is poured on to aqueous hydrochloric acid (1 M; 50 ml) and the mixture is extracted twice with ethyl acetate (50 ml). The combined organic phases are dried over sodium sulphate, filtered and concentrated. The residue is chromatographed over silica gel with n-hexanelethyl acetate (9/1). The pure fractions are combined and the solvent is evaporated off. [00367] Yield: 5.40 g (98%) as a white solid. [00368] MS: 333 (M) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); at 80℃; | EXAMPLE 1; Step 1; To a solution of 1.0 eq 1A in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPh3)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 80° C. overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on 1A) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica gel using 10percent Et2O/hexane as the eluant provided 1B as a solid (90percent). |
90% | tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; | To a solution of 1.0 eq IA in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPh3)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 800C overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on IA) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by <n="54"/>chromatography over silica gel using 10percent Et2psi/hexane as the eluant provided IB as a solid (90percent). |
90% | tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; | To a solution of 1.0 eq IA in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPli3)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 800C overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on IA) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica gel using 10percent Et2O/hexane as the eluant provided IB as a solid (90percent). |
90% | tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; | To a solution of 1.0 eq IA in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPhj)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 800C overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on IA) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica, gel using 10percent Et2O/hexane as the eluant provided IB as a solid (90percent). |
90% | tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide;Heating / reflux; | Example 1 Step 1. To a solution of 1.0 eq IA in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPlIa)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 800C overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on IA) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica gel using 10percent E_2psi/hexane as the eluant provided IB as a solid (90percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; | EXAMPLE 1; Step 1 To a solution of 1.0 eq 1A in dry DMF (0.37 M) was added Zn(CN)2 (0.92 eq) and Pd(PPh3)4 (0.058 eq). The reaction mixture was purged with nitrogen and heated to 80° C. overnight. An additional 0.023 eq of Pd(PPh3)4 was then added and the reaction was heated for another 6 hrs. The reaction mixture was then cooled to RT, diluted with 15 volumes of EtOAc (based on 1A) and the organic layer was washed 3 times with water and once with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by chromatography over silica gel using 10percent Et2O/hexane as the eluant provided 1B as a solid (90percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) cyanide; In N,N-dimethyl-formamide; | 1) Preparation of 3-Fluoro-5-nitrobenzonitrile Copper cyanide (5.03 g) was dried overnight and mixed with 15.0 g of 1-fluoro-3-iodo-5-nitrobenzene and 120 ml of dimethylformamide. The mixture was heated under reflux for 3 hours. After cooling, the reaction mixture was poured into ice-water containing about 4N hydrochloric acid, followed by stirring vigorously for 1 hour. Ethyl ether was added to the reaction mixture, followed by stirring vigorously for 1.5 hours. The insoluble matter was removed by filtration using Celite, and the filtrate was extracted with ethyl ether repeatedly. The ethyl ether layer was washed with water and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate. The solvent was removed by evaporation. The residue was subjected to silica gel column chromatography using a mixture of hexane-ethyl acetate (50:3 by volume) as an elude. The fraction containing the desired compound was concentrated to afford 8.00 g of the title compound. 1H-NMR (CDCl3) delta: 7.73 (dd, 1H, J=7, 1.5 Hz), 8.21 (dt, J=8, 2 Hz), 8.36 (m, 1H) |
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